[unreadable] Atopic dermatitis (AD) is a common allergic disease seen in 10-20% of infants. While severity often[unreadable] diminishes with age, AD can persist throughout life. Moreover, AD severity can be a predictor of[unreadable] subsequent allergic disease as 60% of children who have AD will develop other atopic diseases, including[unreadable] asthma. Thus, it is often thought that AD is the first step on the "Allergic March" towards more severe atopic[unreadable] disease. While both defects in skin and a predisposition towards a hyper-Th2 response contribute towards[unreadable] AD, it is not clear which is the primary defect in the pathogenesis of AD. Chronic lesions convert to[unreadable] inflammation more characteristic of Th1-mediated immunity though what triggers this switch is unclear. In[unreadable] this AADCRC application, we will define several of the factors that contribute to disease initiation and[unreadable] exacerbation. In Project 1, patient samples and a mouse model of AD resulting from hyper-Th2 responses[unreadable] will be used to determine which cytokine and signaling pathways correlate with, or are required for, AD[unreadable] development. The mouse model of AD will also be used to define the effects of AD concurrent with the[unreadable] development of other atopic diseases. Project 2 will examine the contribution of dendritic cells as mediators[unreadable] of innate immunity in the development of AD by examining the function of DC populations in patient samples[unreadable] and mice that have AD and their ability to direct either Th2 or Th1 dependent immunity. Project 3 will[unreadable] qualitatively and quantitatively define bacteria and bacterial products from infected AD lesions. The role of[unreadable] the lipid mediator platelet-activating factor (PAF) and toll-like receptors in bacterial product-mediated[unreadable] inflammation and immunomodulation will be assessed both in vitro as well as in vivo using cellular and[unreadable] murine models. These three projects, supported by an Administrative and Resources Cores, are highly[unreadable] interactive and interrelated. The focus of this application, coupled with the complementary backgrounds of[unreadable] each of the Project Directors, provide a scientific environment poised to make rapid progress in defining the[unreadable] roles of immune components in Atopic Dermatitis.[unreadable] Lay summary-Atopic dermatitis is a very common allergic disorder affecting 10-20% of infants. While it is[unreadable] not a life-threatening disease, it is a source of great discomfort and can have adverse effects on social and[unreadable] emotional development. Additionally, it is a strong indication for the development of other allergic diseases[unreadable] later in life, including asthma. This proposal examines the development of atopic dermatitis and how[unreadable] development may impact other allergic diseases.[unreadable]